Anifrolumab in Adults With Primary Antiphospholipid Syndrome (AnifAPS Trial) (AnifAPS)

A Phase II Open-Label Pilot Trial Assessing the Safety of Anifrolumab in Adult Patients With Primary Antiphospholipid Syndrome (APS). The AnifAPS Trial

This is a phase II, single-centre, open-label pilot study evaluating the safety and tolerability of anifrolumab in adult patients with primary antiphospholipid syndrome (APS). Approximately 20 participants will receive 120 mg subcutaneous anifrolumab once weekly for up to 52 weeks in addition to their standard of care treatment.

The primary objective is to assess the incidence of adverse events during treatment. Secondary and exploratory objectives include evaluation of immunological parameters, thromboinflammatory markers, and patient-reported outcomes. Participants will be followed for an additional 12-week safety follow-up period after completion of treatment.

Study Overview

• Status: Recruiting
• Conditions: Antiphospholipid Syndrome (APS)
• Intervention / Treatment: Drug: Anifrolumab

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Maria G Tektonidou, MD, PhD; Phone Number: +302107462636; Email: mtektonidou@gmail.com

Study Locations

• Greece
  • Greece
    • Athens, Greece, Greece, 11524
      • Recruiting
      • Laiko General Hospital
      • Contact: Maria G Tektonidou, Professor; Phone Number: +302107462636; Email: mtektonidou@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Provision of written informed consent (ICF) prior to any study-specific procedures.
2. Females/males aged 18 to 70 years at Screening (at the time of ICF signing).
3. Weight ≥40.0 kg at Screening.

4. Classified as having primary APS as per the 2023 ACR/EULAR APS classification criteria, i.e. fulfilling at least one documented clinical criterion [ie., macrovascular (venous thromboembolism and/or arterial thrombosis), established microvascular (livedoid vasculopathy, aPL nephropathy, pulmonary haemorrhage or myocardial disease), cardiac valve (valve thickening or valve vegetation) and/or haematology (thrombocytopenia)] and at least one laboratory criterion and scoring at least three points in each of the clinical and laboratory domains.

   Note: Patients with obstetric manifestations will be excluded from this study.

5. For females of childbearing potential only: Negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test at Screening.
6. Females of childbearing potential must be willing to use a highly effective method of contraception (failure rate of <1% per year when used consistently and correctly) throughout their participation in the study, i.e., from Screening and for up to 20 weeks after the last dose of IP. Examples of highly effective methods of contraception are located in Appendix C, Contraceptive and Barrier Guidance.
7. Male patients who are sexually active with a female partner of childbearing potential must be willing to use a condom (with spermicide where commercially available) throughout their participation in the study, i.e., from Screening and for up to 20 weeks after the last dose of IP.
8. Male patients must not donate sperm during the course of the study and for up to 20 weeks after the last dose of the IP.

9. Meeting all the following TB criteria:

   1. No history of latent or active TB prior to Screening, except for latent TB with documented completion of appropriate treatment as per local SoC Note: Subjects with no history of latent TB prior to the initial Screening visit, but who are diagnosed with latent TB during the Screening Period, may be considered eligible if appropriate treatment is initiated prior to first administration of IP as per local SoC. Such subjects may be re-screened if necessary to allow for local guidelines on latent TB treatment initiation.
   2. No signs or symptoms suggestive of active TB from medical history or physical examination
   3. No recent contact with a person with active TB OR if there has been such contact, referral to a physician specialising in TB to undergo additional evaluation prior to first administration of IP (documented appropriately in source), and, if warranted, receipt of appropriate treatment for latent TB at or prior to first administration of IP as per local SoC.
   4. Must meet 1 of the following criteria:

   (i)Negative QuantiFERON-TB Gold (QFT-G) test result for TB obtained within 4 weeks prior to Week 0 (Day 1) OR (ii)Positive QFT-G test result for TB obtained during the Screening Period for which active TB has been ruled out and appropriate treatment for latent TB has been initiated prior to first administration of IP as per local SoC OR (iii)Indeterminate (confirmed on retest) QFT-G test result for TB obtained during the Screening Period with ongoing QFT-G testing for TB as clinically indicated.

10. Chest x-ray [or lung CT*, where available] with no evidence of current active infection (eg, TB) or previous old active TB, malignancy, or clinically significant abnormalities (unless due to APS) obtained during the Screening Period or anytime within 12 weeks prior to signing the ICF.
11. Negative SARs-CoV-2 polymerase chain reaction (PCR) or antigen test result as per local policies at Screening.
12. Females with an intact cervix must have documentation of a normal Pap smear with no documented malignancy (e.g., cervical intraepithelial neoplasia grade III [CIN III], carcinoma in situ [CIS], or adenocarcinoma in situ [AIS]) within 2 years prior to Week 0 (Day 1) (see Appendix E for guidance on abnormal Pap smear results).

Note: Any abnormal Pap smear result documented within 2 years prior to randomisation must be repeated to confirm patient eligibility. See also Exclusion criterion 23b.

Exclusion Criteria:

• General exclusion criteria:

  1. Any condition that, in the opinion of the Investigator, would interfere with the efficacy or safety evaluation of the study intervention or put the participant at safety risk.
  2. Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site).
  3. Current participation in another clinical study with an IP.
  4. Lactating or pregnant females or females who intend to become pregnant anytime from initiation of Screening through the Safety Follow-up Period (12 weeks following last dose of IP).
  5. Current alcohol, drug or chemical abuse, or a history of such abuse within 12 months prior to Week 0 (Day 1).
  6. Major surgery within 8 weeks prior to Screening or elective major surgery planned anytime from initiation of Screening through the Safety Follow-up Period (12 weeks following last dose of IP).
  7. Spontaneous or induced abortion, still or live birth, or pregnancy ≤4 weeks prior to Screening.

  8. Any of the following laboratory abnormalities at Screening (within 4 weeks prior to Week 0 [Day 1]):

     • aspartate aminotransferase (AST) >2.5 x upper limit of normal (ULN)
     • alanine aminotransferase (ALT) >2.0 x ULN
     • total bilirubin > ULN (unless due to Gilbert's syndrome)
     • serum creatinine >2.5 mg/dL (or >181 μmol/L)
     • urine protein/creatinine ratio (UACR) >2.0 mg/mg (or >226.30 mg/mmol)
     • neutrophil count <1000/μL (or <1.0 x 109/L)
     • PLT <25000/ μL (or <25 x 109/L)
     • haemoglobin <8 g/dL (or <80 g/L)
     • glycosylated haemoglobin (HbA1c) >8% (or >0.08) for diabetic subjects only Note: Abnormal screening laboratory tests may be repeated once on a separate sample before the subject is declared a screen failure.

  9. Major surgery within 8 weeks prior to Screening or elective major surgery planned anytime from initiation of Screening through the Safety Follow-up Period (12 weeks following last dose of IP).

     Exclusion criteria related to APS and/or other medical conditions/diseases:

  10. Meeting ACR/EULAR classification criteria for SLE or other systemic autoimmune diseases.
  11. History or current diagnosis of catastrophic APS within 12 months prior to Screening.
  12. Any medical or psychiatric condition (including severe or unstable neuropsychiatric APS) that, in the opinion of the Investigator, could jeopardize or would compromise the study participant's ability to participate in this study.
  13. Current evidence of moderately severe depression as indicated by a score ≥15 in the PHQ-9 questionnaire at Screening.

  14. Known history of suicidal behaviour in the past 12 months prior to Screening or current evidence of suicidal ideation as indicated by a positive response (i.e., selecting 1: "Several days", 2: "More than half the days" or 3: "Nearly every day") to Question 9 of the PHQ-9 questionnaire irrespective of total score at Screening.

      Exclusion criteria related to infection and malignancy risk factors:

  15. Known history of a primary immunodeficiency, splenectomy, or any underlying condition that predisposes the subject to infection or a positive result for humanimmunodeficiency virus (HIV) antibody or infection confirmed by the local laboratory at Screening.

      Note: An HIV test must be performed during the Screening Period, and the result should be available prior to Week 0 (Day 1). Patients refusing to perform HIV testing during the Screening Period will be excluded from study participation.

  16. Confirmed seropositivity for hepatitis B at Screening, i.e.:

      1. Positive result for hepatitis B surface antigen (HBsAg), OR
      2. Positive result for hepatitis B core antibody (HBcAb) AND hepatitis B virus (HBV) DNA detected above the lower limit of quantification (LLQ) by reflex testing by the local laboratory.

      Note: Patients who are HBcAb-positive at Screening will be tested every 3 months for HBV DNA. To remain eligible for the study, the patient's HBV DNA levels must remain below the LLQ as per the local laboratory.

  17. Positive result for hepatitis C antibody at Screening.
  18. Any severe herpes zoster infection at any time prior to Week 0 (Day 1), including but not limited to, non-cutaneous herpes (ever), herpes encephalitis (ever), recurrent herpes zoster (defined as 2 episodes within 2 years) or ophthalmic herpes involving the retina (ever).
  19. Any herpes zoster, cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infection that has not completely resolved within 12 weeks prior to Screening.
  20. Any history of severe COVID-19 infection or any prior COVID-19 infection with documented long-COVID and/or clinically significant unresolved sequelae within 12 months prior to Week 0 (Day 1) or mild/asymptomatic acute COVID-19 infection (lab confirmed or suspected based on clinical signs/symptoms) within 6 weeks prior to Week 0 (Day 1).
  21. Any opportunistic infection requiring hospitalisation or treatment with IV antibiotics within 3 years prior to Screening.

  22. Any of the following:

      1. Clinically significant chronic infection (e.g. osteomyelitis, bronchiectasis, etc.) within 8 weeks prior to Week 0 (Day 1) (chronic nail infections are allowed)
      2. Any infection requiring hospitalization or treatment with IV antibiotics not completed at least 4 weeks prior to Week 0 (Day 1)
  23. Any infection requiring oral antibiotics (including antivirals) within 2 weeks prior to Week 0 (Day 1).

  24. History of malignancy except for:

      1. squamous or basal cell carcinoma of the skin with documented success of curative therapy of ≥3 months prior to Week 0 (Day 1), OR
      2. cervical cancer in situ (CIS) treated with documented success of curative therapy ≥12 months prior to Week 0 (Day 1)

      Exclusion criteria related to prior/concomitant medications:

  25. Currently receiving direct oral anticoagulants (DOACs).

  26. Prior treatment with any of the following:

      • anifrolumab
      • any investigational product (small molecule or biologic agent) within 90 days or 5 half-lives prior to Screening, whichever is greater
      • any commercially available biologic agent, including but not limited to B-cell depleting therapies [i.e. rituximab, other anti-CD20, anti-CD22 or anti-CD38 agents], anti-TNF-α agents, belimumab, abatacept or any other, within 90 days or 5 half-lives prior to Screening, whichever is greater
      • any commercially available protein kinase inhibitor including but not limited to Janus kinase (JAK) inhibitors or Bruton's tyrosine kinase (BTK) inhibitors within 90 days or 5 half-lives prior to Screening, whichever is greater
      • conventional immunomodulators or immunosuppressants (e.g., cyclophosphamide, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, etc.) or IV immunoglobulin within 90 days prior to Screening
      • intraarticular, intramuscular, or intravenous corticosteroids within 30 days prior to Screening.
      • any live or attenuated vaccine within 8 weeks prior to Screening.
  27. Current treatment with oral corticosteroids except for patients with severe thrombocytopenia or pulmonary haemorrhage who have started oral corticosteroids (up to 40 mg/day prednisone or equivalent) within 30 days Week 0 (Day 1).
  28. Blood transfusion or receipt of blood products within 4 weeks prior to Screening.
  29. Known history of allergy or reaction to any component of the IP formulation or history of anaphylaxis to any human gamma globulin therapy.

For procedures for withdrawal of incorrectly enrolled subjects, see Section 3.4.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Anifrolumab + Standard of Care; Participants receive 120 mg subcutaneous anifrolumab once weekly for up to 52 weeks in addition to their ongoing standard of care treatment for primary antiphospholipid syndrome. After completion of treatment, participants enter a 12-week safety follow-up period.	Drug: Anifrolumab; Anifrolumab 120 mg administered subcutaneously once weekly for up to 52 weeks in addition to standard of care treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of anifrolumab	Incidence of adverse events (AEs) including adverse events of special interest [AESIs; i.e., opportunistic infections, serious non-opportunistic infections, herpes zoster, influenza, malignancies, anaphylaxis]	by week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacodynamics (PD) of anifrolumab	Change from baseline (neutralization rate) in type I IFN signature, as assessed by a validated 4-gene panel at weeks 24 and 52	baseline-week 24-week 52
Effect of anifrolumab on the patient's immunological profile	Change from baseline in aCL and aβ2GPI IgG antibody titres at weeks 12, 24 and 52	from baseline to weeks 12, 24 and 52
Effect of anifrolumab on the patients' immunological profile	Change from baseline in lupus anticoagulant (LA) status at weeks 24 and 52	from baseline to weeks 24 and 52
Effect of anifrolumab on the patient's immunological profile	Change from baseline in complement C3 and C4 levels at weeks 12, 24 and 52	from baseline to weeks 12, 24 and 52
Effect of anifrolumab on thrombin generation	Change from baseline in endogenous thrombin potential, as assessed by a thrombin generation assay at weeks 24 and 52	from baseline to weeks 24 and 52
Effect of anifrolumab on neutrophil extracellular trap (NET) release	Change from baseline in the levels of ΝET release markers [i.e., myeloperoxidase (MPO), citrullinated histone H3 (H3Cit) and MPO-deoxyribonucleic acid (DNA) complexes), as assessed by immunofluorescence confocal microscopy and enzyme-linked immunosorbent assay (ELISA) at weeks 24 and 52	from baseline to weeks 24 and 52
The effect of anifrolumab on thromboinflammation-related gene expression	Change from baseline in immunothrombosis/thromboinflammation-related gene expression, as assessed by bulk ribonucleic acid (RNA) sequencing at weeks 24 and 52	from baseline to weeks 24 and 52
The effect of anifrolumab on health-related quality of life (HRQL) and other patient-reported outcomes (PROs)	Change from baseline in the 36-Item Short Form Survey version 2 (SF-36v2) score at weeks 4, 12, 24, 36, 48 and 52	From baseline to weeks 4, 12, 24, 36, 48 and 52
The effect of anifrolumab on health-related quality of life (HRQL) and other patient-reported outcomes (PROs)	Change from baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) score at weeks 4, 12, 24, 36, 48 and 52	From baseline to weeks 4, 12, 24, 36, 48 and 52
The effect of anifrolumab on health-related quality of life (HRQL) and other patient-reported outcomes (PROs)	Change from baseline in the Patient Health Questionnaire 9 (PHQ-9) score at weeks 4, 12, 24, 36,48 and 52	From baseline to weeks 4, 12, 24, 36,48 and 52
The effect of anifrolumab on health-related quality of life (HRQL) and other patient-reported outcomes (PROs)	Change from baseline in the Patient's Global Assessment of health status (PtGA) score at weeks 4, 12, 24, 36, 48 and 52	From baseline to weeks 4, 12, 24, 36, 48 and 52
Physician's global assessment of patient's health status	Change from baseline in the Physician's Global Assessment of patient's health status (PhGA) score at weeks 4, 12, 24, 36, 48 and 52	From baseline to weeks 4, 12, 24, 36, 48 and 52

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the efficacy of anifrolumab in the prevention of recurrent thrombotic APS events	Rate of recurrent venous or arterial thrombotic events in patients with thrombotic APS by week 52	By week 52
Evaluate the efficacy of anifrolumab in livedoid vasculopathy/skin ulcers	Proportion of patients with livedoid vasculopathy/skin ulcers at baseline achieving complete, partial or no response (as defined in the protocol) by week 52	by week 52
Evaluate the efficacy of anifrolumab in APS nephropathy features	Proportion of patients with APS nephropathy at baseline achieving complete, partial or no response (as defined in the protocol) by week 52	week 52
The efficacy of anifrolumab in pulmonary haemorrhage	Proportion of patients with pulmonary haemorrhage at baseline achieving complete, partial or no response (as defined in the protocol) by week 52	By week 52
Efficacy of anifrolumab in myocardial disease	Proportion of patients with myocardial disease at baseline achieving complete, partial or no response (as defined in the protocol) by week 52	by week 52
The efficacy of anifrolumab in thrombocytopenia	Proportion of patients with thrombocytopenia at baseline achieving complete, partial or no response (as defined in the protocol) by week 52.	week 52

Collaborators and Investigators

• Sponsor: National and Kapodistrian University of Athens
• Collaborators: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: May 7, 2026
• First Submitted That Met QC Criteria: May 7, 2026
• First Posted (Actual): May 13, 2026

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 30, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Autoimmune Diseases; Immune System Diseases; Antiphospholipid Syndrome; anifrolumab
• Other Study ID Numbers: ESR-23-22244; 2025-520918-64-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No